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J Immunol. 2012 Aug 1;189(3):1123-7. doi: 10.4049/jimmunol.1200695. Epub 2012 Jul 2.

Cutting edge: CTLA-4 on effector T cells inhibits in trans.

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Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.


CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells (Tregs). We studied in vivo responses of normal and CTLA-4-deficient Ag-specific murine effector CD4(+) T cells. We directly demonstrate that effector T cell-restricted CTLA-4 inhibits T cell responses in a cell-extrinsic manner. Cotransfer experiments show that CTLA-4 on normal effector CD4(+) T cells completely abrogates the dramatically increased expansion normally experienced by their CTLA-4-deficient counterparts. Neither the wild-type nor the CTLA-4-deficient T cells express the Treg transcription factor Foxp3 when transferred alone or together. Thus, cell-extrinsic inhibition of T cell responses by CTLA-4 is not limited to Tregs but is also a function of effector T cells.

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